title: Activation of heme oxygenase recovers motor function after spinal cord injury in rats.
abstract: Characterization of auto-destructive mechanisms, leading to cell death after spinal cord injury (SCI) is important to prevent further damage to tissue. Heme oxygenase (HO) catalyzes the oxidation of heme to biliverdin and carbon monoxide (CO), as a response to cell damage. Products of HO action have biological effects, as antioxidant biliverdin. We evaluated the changes of HO activity after injury, and the effect of pharmacological treatments with hemin (an inducer) and (Sn)-protoporphyrin (an inhibitor, Sn-PPIX) of HO, upon motor recovery after SCI. Female Wistar rats were submitted to SCI by trauma and sacrificed at several times (2, 4, 8, 12 and 24h) after injury to evaluate HO activity. Additional groups of rats were treated with either hemin or Sn-PPIX, to evaluate motor recovery, spared spinal cord tissue and HO activity. Results showed that HO control activity was increased by effect of SCI, at all times evaluated, as compared to sham group values. Twenty-four hours after injury, HO activity was increased 7.2-fold by hemin treatment, as compared to SCI plus vehicle group values. In addition, animals treated with hemin 2 and 8h after SCI, showed a better motor recovery and higher spared cord tissue, as compared to control group values. Our findings indicate that activation of HO is a beneficial mechanism when attained during the acute phase after SCI.
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A., México, Mexico.
authors.forename: Araceli
authors.initials: A
authors.lastname: Diaz-Ruiz
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Marisela
authors.initials: M
authors.lastname: Mendez-Armenta
authors.forename: Karla
authors.initials: K
authors.lastname: Jiménez-García
authors.forename: Hermelinda
authors.initials: H
authors.lastname: Salgado-Ceballos
authors.forename: Ivan
authors.initials: I
authors.lastname: Santander
authors.forename: Camilo
authors.initials: C
authors.lastname: Ríos
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004790:Enzyme Induction; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D009048:Motor Skills; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D008665:Metalloporphyrins; D011524:Protoporphyrins; D006427:Hemin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing)
keywords: (Sn)-protoporphyrin; BBB score; Heme oxygenase; Hemin; Spinal cord injury